Druker Jimena, Liberman Ana C, Acuña Matías, Giacomini Damiana, Refojo Damián, Silberstein Susana, Pereda Marcelo Paez, Stalla Günter K, Holsboer Florian, Arzt Eduardo
Laboratorio de Fisiología y Biología Molecular, Departmento de Fisiologiía y Biooogía Molecular y Celular, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.
Ann N Y Acad Sci. 2006 Nov;1088:297-306. doi: 10.1196/annals.1366.007.
Highly sophisticated mechanisms confer upon the immune system the capacity to respond with a certain degree of autonomy. However, the final outcome of an adaptative immune response depends on the interaction with other systems of the organism. The immune-neuroendocrine systems have an intimate cross-communication, making possible a satisfactory response to environmental changes. Part of this interaction occurs through cytokines and steroid hormones. The last step of this crosstalk is at the molecular level. In this article we will focus on the physical and functional interrelationship between cytokine signaling pathway-activated transcription factors (TFs) and steroid receptors in different cell models, where the signals triggered by cytokines and steroid hormones have major roles: (1) the ligand-dependent-activated glucocorticoid receptor (GR) influence the genetic program that specifies lineage commitment in T helper (Th) cell differentiation. How posttranslational modifications of several TFs as well as nuclear hormone receptors could be implicated in the molecular crosstalk between the immune-neuroendocrine messengers is discussed. (2) glucocorticoid (GC) antagonism on the TCR-induced T cell apoptosis. (3) estrogen receptor/TGF-beta family proteins molecular interaction implicated on pituitary prolactinomas pathogenesis. The functional crosstalk at the molecular level between immune and steroids signals is essential to determine an integrative response to both mediators (which in the last instance results in a new gene activation/repression profile) and constitutes the ultimate integrative level of interaction between the immune and neuroendocrine systems.
高度复杂的机制赋予免疫系统一定程度的自主反应能力。然而，适应性免疫反应的最终结果取决于与机体其他系统的相互作用。免疫-神经内分泌系统存在密切的相互交流，使得对环境变化能够做出令人满意的反应。这种相互作用的一部分是通过细胞因子和类固醇激素发生的。这种相互作用的最后一步发生在分子水平。在本文中，我们将聚焦于不同细胞模型中细胞因子信号通路激活的转录因子（TFs）与类固醇受体之间的物理和功能相互关系，在这些模型中细胞因子和类固醇激素触发的信号起着主要作用：（1）配体依赖性激活的糖皮质激素受体（GR）影响在辅助性T（Th）细胞分化中决定谱系定向的遗传程序。讨论了几种转录因子以及核激素受体的翻译后修饰如何参与免疫-神经内分泌信使之间的分子相互作用。（2）糖皮质激素（GC）对TCR诱导的T细胞凋亡的拮抗作用。（3）雌激素受体/TGF-β家族蛋白的分子相互作用与垂体催乳素瘤的发病机制有关。免疫和类固醇信号在分子水平上的功能相互作用对于确定对两种介质的综合反应（最终导致新的基因激活/抑制谱）至关重要，并且构成了免疫和神经内分泌系统之间相互作用的最终整合水平。
